Chlamydia trachomatis is a major cause of sexually transmitted disease (STD). Infections of women can cause salpingitis which results in chronic abdominal pain, tubal occlusion, and infertility. The cost of treating chlamydial salpingitis in the U.S. alone is estimated to be $2.5 billion per year and as many as 50,000 women per year become infertile as a result of chlamydial infection. Moreover, chlamydial infection has recently been shown to increase the risk of acquiring HIV by as much as 50% in high risk populations. Immunoprophylaxis is a primary strategy for preventing chlamydial STD~s however, little progress has been made toward this goal due to a lack of understanding of the hosts immune response to chlamydial infection. The goal of this project is to utilize a mouse model for the study of adaptive immunity to chlamydial infection of the female genital tract. The objectives of the work are to (I) delineate the immunological basis of protective immunity, (ii) define and characterize thos chlamydial antigens that elicit protective immune responses, and (iii) develop recombinant subunit or DNA based vaccines capable of preventing or reducing sequelae of infection that result in chronic disease. Previous studieis have implicated secretory IgA, CD8+, and CD4+ T cells as components of the protective immune response to C. Trachomatis infection of the genital tract. We have shown that chlamydial clearance is unaffected in knockout mice deficient in the gene (B-cell deficient) or microglobulin gene (lack functional CD8+T-cells). In contrast, MHC class II knockout mice lacking those molecules required for presentation of antigen to CD4+ T cells failed to clear genital chlamydial infections, demonstrating the essential role of CD4+ T cells in host resistance. The importance of CD4+ T cells inprotective immunity to chlamydial infection was also demonstrated by adoptive immunization experiments using immune CD4+ and CD8+ T cells. Antibody-mediated in vivo neutralization of IL-12 was associated with a significant delay in clearance (Perry, Z01 AI 00735-01) while abrogation of IL-4 activity resulted in clearance rates similar to controls, implicating a dominant role for Th1 mediated immunity in host resistance to chlamydial infection of the genital tract.